title: Comparison of intradermal and intramuscular delivery followed by in vivo electroporation of SIV Env DNA in macaques.
abstract: A panel of SIVmac251 transmitted Env sequences were tested for expression, function and immunogenicity in mice and macaques. The immunogenicity of a DNA vaccine cocktail expressing SIVmac239 and three transmitted SIVmac251 Env sequences was evaluated upon intradermal or intramuscular injection followed by in vivo electroporation in macaques using sequential vaccination of gp160, gp120 and gp140 expressing DNAs. Both intradermal and intramuscular vaccination regimens using the gp160 expression plasmids induced robust humoral immune responses, which further improved using the gp120 expressing DNAs. The responses showed durability of binding and neutralizing antibody titers and high avidity for>1 y. The intradermal DNA delivery regimen induced higher cross-reactive responses able to neutralize the heterologous tier 1B-like SIVsmE660_CG7V. Analysis of cellular immune responses showed induction of Env-specific memory responses and cytotoxic granzyme B(+) T cells in both vaccine groups, although the magnitude of the responses were ~10x higher in the intramuscular/electroporation group. The cellular responses induced by both regimens were long lasting and could be detected ~1 y after the last vaccination. These data show that both DNA delivery methods are able to induce robust and durable immune responses in macaques.
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Viraj
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Margherita
authors.initials: M
authors.lastname: Rosati
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Jenifer
authors.initials: J
authors.lastname: Bear
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Guy R
authors.initials: GR
authors.lastname: Pilkington
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Jalah
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bergamaschi
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Candido
authors.initials: C
authors.lastname: Alicea
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Bhabadeb
authors.initials: B
authors.lastname: Chowdhury
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA; Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Gen-Mu
authors.initials: GM
authors.lastname: Zhang
authors.affiliation: Division of Infectious Diseases; The Feinberg School of Medicine; Northwestern University; Chicago, IL USA.
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Division of Infectious Diseases; The Feinberg School of Medicine; Northwestern University; Chicago, IL USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Wolinsky
authors.affiliation: Institute of Human Virology; Department of Microbiology and Immunology; University of Maryland School of Medicine; Baltimore, MD USA.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Huang
authors.affiliation: Institute of Human Virology; Department of Microbiology and Immunology; University of Maryland School of Medicine; Baltimore, MD USA.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Surgery; Laboratory for AIDS Vaccine Research and Development; Duke University Medical Center; Durham, NC USA.
authors.forename: Celia
authors.initials: C
authors.lastname: LaBranche
authors.affiliation: Department of Surgery; Laboratory for AIDS Vaccine Research and Development; Duke University Medical Center; Durham, NC USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Inovio Pharmaceuticals, Inc.; Blue Bell, PA USA.
authors.forename: Kate E
authors.initials: KE
authors.lastname: Broderick
authors.affiliation: Inovio Pharmaceuticals, Inc.; Blue Bell, PA USA.
authors.forename: Niranjan Y
authors.initials: NY
authors.lastname: Sardesai
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Felber
authors.affiliation: Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
authors.forename: George N
authors.initials: GN
authors.lastname: Pavlakis
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D018274:Electroporation / Q000379:methods*; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015686:Gene Products, env; D018449:SAIDS Vaccines; D019444:Vaccines, DNA
keywords: DNA vaccine; HIV; SIVmac239; SIVmac251; SIVsmE660; avidity; binding antibody; effector memory; in vivo electroporation; intradermal; intramuscular; neutralizing antibody; transitional memory; transmitted Env